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Interplay between the Kinesin and Tubulin Mechanochemical Cycles Underlies Microtubule Tip Tracking by the Non-motile Ciliary Kinesin Kif7.

Jiang S, Mani N, Wilson-Kubalek EM, Ku PI, Milligan RA, Subramanian R
Dev Cell 49 711-730.e8 (2019)
Cited: 9 times
EuropePMC logo PMID: 31031197

Abstract

The correct localization of Hedgehog effectors to the tip of primary cilia is critical for proper signal transduction. The conserved non-motile kinesin Kif7 defines a "cilium-tip compartment" by localizing to the distal ends of axonemal microtubules. How Kif7 recognizes microtubule ends remains unknown. We find that Kif7 preferentially binds GTP-tubulin at microtubule ends over GDP-tubulin in the mature microtubule lattice, and ATP hydrolysis by Kif7 enhances this discrimination. Cryo-electron microscopy (cryo-EM) structures suggest that a rotated microtubule footprint and conformational changes in the ATP-binding pocket underlie Kif7's atypical microtubule-binding properties. Finally, Kif7 not only recognizes but also stabilizes a GTP-form of tubulin to promote its own microtubule-end localization. Thus, unlike the characteristic microtubule-regulated ATPase activity of kinesins, Kif7 modulates the tubulin mechanochemical cycle. We propose that the ubiquitous kinesin fold has been repurposed in Kif7 to facilitate organization of a spatially restricted platform for localization of Hedgehog effectors at the cilium tip.

Articles - 6mlq mentioned but not cited (2)

  1. Interplay between the Kinesin and Tubulin Mechanochemical Cycles Underlies Microtubule Tip Tracking by the Non-motile Ciliary Kinesin Kif7. Jiang S, Mani N, Wilson-Kubalek EM, Ku PI, Milligan RA, Subramanian R. Dev Cell 49 711-730.e8 (2019)
  2. Cytoskeletal regulation of a transcription factor by DNA mimicry via coiled-coil interactions. Haque F, Freniere C, Ye Q, Mani N, Wilson-Kubalek EM, Ku PI, Milligan RA, Subramanian R. Nat Cell Biol 24 1088-1098 (2022)


Reviews citing this publication (2)

  1. Developmental and regenerative paradigms of cilia regulated hedgehog signaling. Kopinke D, Norris AM, Mukhopadhyay S. Semin Cell Dev Biol 110 89-103 (2021)
  2. Emerging mechanistic understanding of cilia function in cellular signalling. Hilgendorf KI, Myers BR, Reiter JF. Nat Rev Mol Cell Biol (2024)

Articles citing this publication (5)

  1. Biallelic loss of function NEK3 mutations deacetylate α-tubulin and downregulate NUP205 that predispose individuals to cilia-related abnormal cardiac left-right patterning. Zhang Y, Chen W, Zeng W, Lu Z, Zhou X. Cell Death Dis 11 1005 (2020)
  2. Differential regulation of single microtubules and bundles by a three-protein module. Mani N, Jiang S, Neary AE, Wijeratne SS, Subramanian R. Nat Chem Biol 17 964-974 (2021)
  3. Sequences in the stalk domain regulate auto-inhibition and ciliary tip localization of the immotile kinesin-4 KIF7. Blasius TL, Yue Y, Prasad R, Liu X, Gennerich A, Verhey KJ. J Cell Sci 134 jcs258464 (2021)
  4. Structural model of microtubule dynamics inhibition by kinesin-4 from the crystal structure of KLP-12 -tubulin complex. Taguchi S, Nakano J, Imasaki T, Kita T, Saijo-Hamano Y, Sakai N, Shigematsu H, Okuma H, Shimizu T, Nitta E, Kikkawa S, Mizobuchi S, Niwa S, Nitta R. Elife 11 e77877 (2022)
  5. Hedgehog-induced ciliary trafficking of kinesin-4 motor KIF7 requires intraflagellar transport but not KIF7's microtubule binding. Yue Y, Engelke MF, Blasius TL, Verhey KJ. Mol Biol Cell 33 br1 (2022)


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